Wo 2010/040571 A2

Total Page:16

File Type:pdf, Size:1020Kb

Wo 2010/040571 A2 (12) INTERNATIONAL APPLICATION PUBLISHED UNDER THE PATENT COOPERATION TREATY (PCT) (19) World Intellectual Property Organization International Bureau (10) International Publication Number (43) International Publication Date 15 April 2010 (15.04.2010) WO 2010/040571 A2 (51) International Patent Classification: (81) Designated States (unless otherwise indicated, for every C12N 15/11 (2006.01) kind of national protection available): AE, AG, AL, AM, AO, AT, AU, AZ, BA, BB, BG, BH, BR, BW, BY, BZ, (21) International Application Number: CA, CH, CL, CN, CO, CR, CU, CZ, DE, DK, DM, DO, PCT/EP2009/00743 1 DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, GT, (22) International Filing Date: HN, HR, HU, ID, IL, IN, IS, JP, KE, KG, KM, KN, KP, 12 October 2009 (12.10.2009) KR, KZ, LA, LC, LK, LR, LS, LT, LU, LY, MA, MD, ME, MG, MK, MN, MW, MX, MY, MZ, NA, NG, NI, (25) Filing Language: English NO, NZ, OM, PE, PG, PH, PL, PT, RO, RS, RU, SC, SD, (26) Publication Language: English SE, SG, SK, SL, SM, ST, SV, SY, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, ZA, ZM, ZW. (30) Priority Data: 08075816.2 10 October 2008 (10.10.2008) DE (84) Designated States (unless otherwise indicated, for every kind of regional protection available): ARIPO (BW, GH, (71) Applicant (for all designated States except US): GM, KE, LS, MW, MZ, NA, SD, SL, SZ, TZ, UG, ZM, FRAUNHOFER-GESELLSCHAFT ZUR ZW), Eurasian (AM, AZ, BY, KG, KZ, MD, RU, TJ, FORDERUNG DER ANGEWANDTEN TM), European (AT, BE, BG, CH, CY, CZ, DE, DK, EE, FORSCHUNG E.V. [DE/DE]; Hansastr. 27 c, 80686 ES, FI, FR, GB, GR, HR, HU, IE, IS, IT, LT, LU, LV, Mϋnchen (DE). MC, MK, MT, NL, NO, PL, PT, RO, SE, SI, SK, SM, TR), OAPI (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, (72) Inventors; and ML, MR, NE, SN, TD, TG). (75) Inventors/Applicants (for US only): BORLAK, Jurgen [DE/DE]; Arpke Str. 12 g, 31275 Lehrte OT Immensen Published: (DE). WELTMEIER, Fridjof [DE/DE]; Schwanenring — without international search report and to be republished 17, 30627 Hannover (DE). upon receipt of that report (Rule 48.2(gf) (74) Agent: BAUMBACH, F.; Robert-Rδssle-Strasse 10, — with sequence listing part of description (Rule 5.2(a)) 13 125 Berlin (DE). (54) Title: METHOD FOR A GENOME WIDE IDENTIFICATION OF EXPRESSION REGULATORY SEQUENCES AND USE OF GENES AND MOLECULES DERIVED THEREOF FOR THE DIAGNOSIS AND THERAPY OF METABOLIC AND/OR TUMOROUS DISEASES (57) Abstract: The invention is directed to the use of particular human genes, nucleic acids hybridizing to said genes, and gene products encoded thereby in the context of the diagnosis and/or therapy of metabolic and/or cancerous diseases, preferably of dia- betes mellitus and/or colorectal cancer, wherein the gene is selected from the group of the human chromosomal genes having at least one expression regulatory sequence according to matrix 1 ("de novo" HNF4αmatrix) in the range of 100000 nucleotides up- stream or downstream of their transcription start site in the human genome, and wherein the at least one expression regulatory se- quence according to matrix 1 is located within the chromosomal position specified by particular start and end sites. The invention further relates to a method for a genomewide identification of functional binding sites at specifically targeted DNA sequences with high resolution, wherein the method comprises, or preferably consists of, the steps of: a) chromatin immunoprecipitation and b) DNA-DNA hybridisation for the c) de novo identification of gene targets. Method for a genome wide identification of expression regulatory sequences and use of genes and molecules derived thereof for the diagnosis and therapy of metabolic and/or tumorous diseases The invention is directed to the use of particular human genes, nucleic acids hybridizing to said genes, and gene products encoded thereby in the context of the diagnosis and/or therapy of metabolic and/or cancerous diseases, preferably of diabetes mellitus and/or colorectal cancer. The invention further relates to a method for a genomewide identification of functional binding sites at specifically targeted DNA sequences with high resolution. Areas of application are the life sciences: biology, biochemistry, biotechnology, medicine and medical technology. Hepatic nuclear factor (HNF)-4 α is a member of the nuclear rece?ptor superfamily and known to be expressed in the liver, intestine, and pancreas (for review see Sladek et al. 2001; Schrem, 2002). Many reports have highlighted the importance of HNF4 α in the regulation of developmental processes in determining the hepatic phenotype, as well as the regulation of diverse metabolic pathways (e.g., glucose, cholesterol, and fatty acid metabolism) (Sladek et al., 1990; Jiang et al., 1995; Yamagata et al., 1996; Hadzopoulou-Cladaras et al., 1997). Therefore, HNF4 α is considered as a hepatic master regulatory protein, ln^contrast to other members of the nuclear receptor superfamily, HNF4α binds to its cognate DNA binding site as a homodimer (Jiang 1997; Sladek 1990). HNF4α is one of the best characterized transcription factors, and in the past some dozent direct binding sites were reported. The employment of ChlP-chip technologies demonstrated however that these are only the smallest fraction of the actual HNF4 α binding sites. Notably, Rada-lglesias et al. (2005) used custom made arrays with a low resolution encompasing the ENCODE regions, i. e. 1% of the genome, for ChlP-chip, and thus mapped 194 HNF4 α binding sites in the human hepatoma cell line HepG2. In another study binding sites in hepatocytes and pancreatic islets were mapped, but the approach focused on promoter regions only (Odom et al, 2004; Odom et al, 2006). Based on the findings published by Rada-lglesias et al. (2005) only a small fraction of HNF4 α binding sites are located in proximal promoter regions. As of today, a genome-wide footprinting of binding sites targeted by HNF4 α has not been reported. However, such a system would allow to identify the common rationale underlying the genome wide regulation processes induced by protein-DNA binding within the context of diseases caused by HNF4 α upregulation, such as adenocarcinomas of the colon may be, namely to identify specific regulatory sequences in the chromosomal genome which (a) bind to HNF4 α and (b) bind to proteins other than HNF4α, wherein said proteins bind to HNF4 α. The aim of the invention is thus to provide a method allowing a genome-wide high resolution map of binding sites relevant for the transcription regulation induced by HNF4 α, and the identification of human chromosomal genes having at least one specific regulatory sequence in their natural environment, and the use of said genes or gene products encoded thereby or of RNA hybridizing to said genes for the diagnosis and therapy of diseases, preferably of adenocarcinomas of the colon, caused by an deregulation of HNF4α To this end, the implementation of the actions and embodiments as described in the claims provides appropriate means to fulfill these demands in a satisfying manner. Thus, the invention in its different aspects and embodiments is implemented according to the claims. In the first aspect, the invention is directed to the use of a human gene, in particular the coding region thereof, or of a gene product encoded thereby or of an antibody directed against said gene product, or of DNA or RNA sequences hybridizing to said gene and coding for a polypeptide having the function of said gene product for the therapy and/or diagnosis of metabolic and/or cancerous diseases and/or to screen for and to identify drugs against metabolic and/or cancerous diseases, such as diabetes mellitus and/or colorectal cancer may be, wherein the gene is selected from the group of the human chromosomal genes having at least one expression regulatory sequence according to matrix 1 ("de novo" HNF4α matrix) in the range of 100000 nucleotides upstream or downstream of their transcription start site in the human genome, and wherein the at least one expression regulatory sequence according to matrix 1 is located within the chromosomal position specified by the start and end sites according to Tables 9-32 (chromosomes 1-22, X-, Y-chromosome, wherein Table 9 refers to the human chromosome 1, Table 10 refers to the human chromosome 2, etc., Table 30 refers to the human chromosome 22, Table 3 1 refers to the human X-chromosome, and Table 32 refers to the human Y-chromosome). The term "gene" according to the invention is directed to both the template strand, which refers to the sequence of the DNA that is copied during the synthesis of mRNA, and to the coding strand corresponding to the codons that are translated into a protein. The genes according to the invention and gene products encoded thereby can be easily derived from the common databases, as such are known to the person skilled in the art, wherein the UCSC Genome Database is particularly preferred: Karolchik D, Kuhn, RM, Baertsch R, Barber GP, Clawson H, Diekhans M, Giardine B, Harte RA, Hinrichs AS1 Hsu F, Miller W , Pedersen JS, Pohl A , Raney BJ, Rhead B, Rosenbloom KR Smith KE, Stanke M, Thakkapallayil A, Trumbower H , Wang T Zweig AS, Haussler D, Kent WJ. The UCSC Genome Browser Database: 2008 update. Nucleic Acids Res. 2008 Jan;36:D773, which is incorporated herein by reference. The term "coding region" according to the invention is directed to the portion of DNA or RNA that is transcribed into the mRNA, which then is translated into a protein. This does not include gene regions such as a recognition site, initiator sequence, or termination sequence.
Recommended publications
  • Download The
    PROBING THE INTERACTION OF ASPERGILLUS FUMIGATUS CONIDIA AND HUMAN AIRWAY EPITHELIAL CELLS BY TRANSCRIPTIONAL PROFILING IN BOTH SPECIES by POL GOMEZ B.Sc., The University of British Columbia, 2002 A THESIS SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF MASTER OF SCIENCE in THE FACULTY OF GRADUATE STUDIES (Experimental Medicine) THE UNIVERSITY OF BRITISH COLUMBIA (Vancouver) January 2010 © Pol Gomez, 2010 ABSTRACT The cells of the airway epithelium play critical roles in host defense to inhaled irritants, and in asthma pathogenesis. These cells are constantly exposed to environmental factors, including the conidia of the ubiquitous mould Aspergillus fumigatus, which are small enough to reach the alveoli. A. fumigatus is associated with a spectrum of diseases ranging from asthma and allergic bronchopulmonary aspergillosis to aspergilloma and invasive aspergillosis. Airway epithelial cells have been shown to internalize A. fumigatus conidia in vitro, but the implications of this process for pathogenesis remain unclear. We have developed a cell culture model for this interaction using the human bronchial epithelium cell line 16HBE and a transgenic A. fumigatus strain expressing green fluorescent protein (GFP). Immunofluorescent staining and nystatin protection assays indicated that cells internalized upwards of 50% of bound conidia. Using fluorescence-activated cell sorting (FACS), cells directly interacting with conidia and cells not associated with any conidia were sorted into separate samples, with an overall accuracy of 75%. Genome-wide transcriptional profiling using microarrays revealed significant responses of 16HBE cells and conidia to each other. Significant changes in gene expression were identified between cells and conidia incubated alone versus together, as well as between GFP positive and negative sorted cells.
    [Show full text]
  • Predicting Clinical Response to Treatment with a Soluble Tnf-Antagonist Or Tnf, Or a Tnf Receptor Agonist
    (19) TZZ _ __T (11) EP 2 192 197 A1 (12) EUROPEAN PATENT APPLICATION (43) Date of publication: (51) Int Cl.: 02.06.2010 Bulletin 2010/22 C12Q 1/68 (2006.01) (21) Application number: 08170119.5 (22) Date of filing: 27.11.2008 (84) Designated Contracting States: (72) Inventor: The designation of the inventor has not AT BE BG CH CY CZ DE DK EE ES FI FR GB GR yet been filed HR HU IE IS IT LI LT LU LV MC MT NL NO PL PT RO SE SI SK TR (74) Representative: Habets, Winand Designated Extension States: Life Science Patents AL BA MK RS PO Box 5096 6130 PB Sittard (NL) (71) Applicant: Vereniging voor Christelijk Hoger Onderwijs, Wetenschappelijk Onderzoek en Patiëntenzorg 1081 HV Amsterdam (NL) (54) Predicting clinical response to treatment with a soluble tnf-antagonist or tnf, or a tnf receptor agonist (57) The invention relates to methods for predicting a clinical response to a therapy with a soluble TNF antagonist, TNF or a TNF receptor agonist and a kit for use in said methods. EP 2 192 197 A1 Printed by Jouve, 75001 PARIS (FR) EP 2 192 197 A1 Description [0001] The invention relates to methods for predicting a clinical response to a treatment with a soluble TNF antagonist, with TNF or a TNF receptor agonist using expression levels of genes of the Type I INF pathway and a kit for use in said 5 methods. In another aspect, the invention relates to a method for evaluating a pharmacological effect of a treatment with a soluble TNF antagonist, TNF or a TNF receptor agonist.
    [Show full text]
  • Association of Gene Ontology Categories with Decay Rate for Hepg2 Experiments These Tables Show Details for All Gene Ontology Categories
    Supplementary Table 1: Association of Gene Ontology Categories with Decay Rate for HepG2 Experiments These tables show details for all Gene Ontology categories. Inferences for manual classification scheme shown at the bottom. Those categories used in Figure 1A are highlighted in bold. Standard Deviations are shown in parentheses. P-values less than 1E-20 are indicated with a "0". Rate r (hour^-1) Half-life < 2hr. Decay % GO Number Category Name Probe Sets Group Non-Group Distribution p-value In-Group Non-Group Representation p-value GO:0006350 transcription 1523 0.221 (0.009) 0.127 (0.002) FASTER 0 13.1 (0.4) 4.5 (0.1) OVER 0 GO:0006351 transcription, DNA-dependent 1498 0.220 (0.009) 0.127 (0.002) FASTER 0 13.0 (0.4) 4.5 (0.1) OVER 0 GO:0006355 regulation of transcription, DNA-dependent 1163 0.230 (0.011) 0.128 (0.002) FASTER 5.00E-21 14.2 (0.5) 4.6 (0.1) OVER 0 GO:0006366 transcription from Pol II promoter 845 0.225 (0.012) 0.130 (0.002) FASTER 1.88E-14 13.0 (0.5) 4.8 (0.1) OVER 0 GO:0006139 nucleobase, nucleoside, nucleotide and nucleic acid metabolism3004 0.173 (0.006) 0.127 (0.002) FASTER 1.28E-12 8.4 (0.2) 4.5 (0.1) OVER 0 GO:0006357 regulation of transcription from Pol II promoter 487 0.231 (0.016) 0.132 (0.002) FASTER 6.05E-10 13.5 (0.6) 4.9 (0.1) OVER 0 GO:0008283 cell proliferation 625 0.189 (0.014) 0.132 (0.002) FASTER 1.95E-05 10.1 (0.6) 5.0 (0.1) OVER 1.50E-20 GO:0006513 monoubiquitination 36 0.305 (0.049) 0.134 (0.002) FASTER 2.69E-04 25.4 (4.4) 5.1 (0.1) OVER 2.04E-06 GO:0007050 cell cycle arrest 57 0.311 (0.054) 0.133 (0.002)
    [Show full text]
  • Effet De La Cryptorchidie Sur Le Transcriptome Testiculaire Humain
    MARIE EVE BERGERON EFFET DE LA CRYPTORCHIDIE SUR LE TRANSCRIPTOME TESTICULAIRE HUMAIN Mémoire présenté à la Faculté des études supérieures et postdoctorales de l’Université Laval dans le cadre du programme de maîtrise en Physiologie-Endocrinologie pour l’obtention du grade de Maître ès sciences (M.Sc.) DÉPARTEMENT D’OBSTÉTRIQUE ET DE GYNÉCOLOGIE FACULTÉ DE MÉDECINE UNIVERSITÉ LAVAL QUÉBEC 2012 © Marie Eve Bergeron, 2012 Résumé Les niveaux d’expression de nombreux gènes peuvent être affectés par l’environnement et mener au développement de la cryptorchidie. Cette malformation congénitale est la plus commune dont une des conséquences majeures est l’infertilité masculine due au testicule non-descendu, auquel un risque plus élevé de cancer testiculaire est associé. L’expression des ARN totaux isolés à partir de biopsies testiculaires ont été analysés par micropuces, puis par une analyse bio-informatique et une validation par RT-qPCR de plusieurs gènes sélectionnés. Ces analyses m’ont permis d’identifier plus de deux milles candidats montrant une expression différente entre des sujets cryptorchides et normaux. Certains de ces gènes sélectionnés peuvent être associés à la descente testiculaire, d’autres au cancer testiculaire ou encore aux divers types cellulaires retrouvés dans cet organe. Les différences dans le transcriptome dues à la cryptorchidie vont nous aider à comprendre la cause génétique de cette maladie. ii Abstract Expression level of numerous genes may be affected by environmental condition and lead to development of cryptorchidism. The most common congenital malformation in male is cryptorchidism. One major consequence of this anomaly is infertility due to undescended testis, to which an increased risk of testicular cancer is associated.
    [Show full text]
  • A Dissertation Entitled the Androgen Receptor
    A Dissertation entitled The Androgen Receptor as a Transcriptional Co-activator: Implications in the Growth and Progression of Prostate Cancer By Mesfin Gonit Submitted to the Graduate Faculty as partial fulfillment of the requirements for the PhD Degree in Biomedical science Dr. Manohar Ratnam, Committee Chair Dr. Lirim Shemshedini, Committee Member Dr. Robert Trumbly, Committee Member Dr. Edwin Sanchez, Committee Member Dr. Beata Lecka -Czernik, Committee Member Dr. Patricia R. Komuniecki, Dean College of Graduate Studies The University of Toledo August 2011 Copyright 2011, Mesfin Gonit This document is copyrighted material. Under copyright law, no parts of this document may be reproduced without the expressed permission of the author. An Abstract of The Androgen Receptor as a Transcriptional Co-activator: Implications in the Growth and Progression of Prostate Cancer By Mesfin Gonit As partial fulfillment of the requirements for the PhD Degree in Biomedical science The University of Toledo August 2011 Prostate cancer depends on the androgen receptor (AR) for growth and survival even in the absence of androgen. In the classical models of gene activation by AR, ligand activated AR signals through binding to the androgen response elements (AREs) in the target gene promoter/enhancer. In the present study the role of AREs in the androgen- independent transcriptional signaling was investigated using LP50 cells, derived from parental LNCaP cells through extended passage in vitro. LP50 cells reflected the signature gene overexpression profile of advanced clinical prostate tumors. The growth of LP50 cells was profoundly dependent on nuclear localized AR but was independent of androgen. Nevertheless, in these cells AR was unable to bind to AREs in the absence of androgen.
    [Show full text]
  • (12) United States Patent (10) Patent No.: US 8.440,393 B2 Birrer Et Al
    USOO8440393B2 (12) United States Patent (10) Patent No.: US 8.440,393 B2 Birrer et al. (45) Date of Patent: May 14, 2013 (54) PRO-ANGIOGENIC GENES IN OVARIAN OTHER PUBLICATIONS TUMORENDOTHELIAL CELL, SOLATES Boyd (The Basic Science of Oncology, 1992, McGraw-Hill, Inc., p. (75) Inventors: Michael J. Birrer, Mt. Airy, MD (US); 379). Tomas A. Bonome, Washington, DC Tockman et al. (Cancer Res., 1992, 52:2711s-2718s).* (US); Anil Sood, Pearland, TX (US); Pritzker (Clinical Chemistry, 2002, 48: 1147-1150).* Chunhua Lu, Missouri City, TX (US) Benedict et al. (J. Exp. Medicine, 2001, 193(1) 89-99).* Jiang et al. (J. Biol. Chem., 2003, 278(7) 4763-4769).* (73) Assignees: The United States of America as Matsushita et al. (FEBS Letters, 1999, vol. 443, pp. 348-352).* Represented by the Secretary of the Singh et al. (Glycobiology, 2001, vol. 11, pp. 587-592).* Department of Health and Human Abbosh et al. (Cancer Res. Jun. 1, 2006 66:5582-55.91 and Supple Services, Washington, DC (US); The mental Figs. S1-S7).* University of MD Anderson Cancer Zhai et al. (Chinese General Practice Aug. 2008, 11(8A): 1366 Center, Houston, TX (US) 1367).* Lu et al. (Cancer Res. Feb. 15, 2007, 64(4): 1757-1768).* (*) Notice: Subject to any disclaimer, the term of this Bagnato et al., “Activation of Mitogenic Signaling by Endothelin 1 in patent is extended or adjusted under 35 Ovarian Carcinoma Cells', Cancer Research, vol. 57, pp. 1306-1311, U.S.C. 154(b) by 194 days. 1997. Bouras et al., “Stanniocalcin 2 is an Estrogen-responsive Gene (21) Appl.
    [Show full text]
  • MIRA-Assisted Microarray Analysis, a New Technology for The
    Research Article MIRA-Assisted Microarray Analysis, a New Technology for the Determination of DNA Methylation Patterns, Identifies Frequent Methylation of Homeodomain-Containing Genes in Lung Cancer Cells Tibor Rauch,1 Hongwei Li,1 Xiwei Wu,2 and Gerd P. Pfeifer1 Divisions of 1Biology and 2Biomedical Informatics, Beckman Research Institute of the City of Hope, Duarte, California Abstract hypermethylation generally leads to inactivation of gene expres- We present a straightforward and comprehensive approach sion, this epigenetic alteration is considered to be a key mechanism for DNA methylation analysis in mammalian genomes. The for long-term silencing of tumor suppressor genes. The importance methylated-CpG island recovery assay (MIRA), which is based of promoter methylation in functional inactivation of lung cancer on the high affinity of the MBD2/MBD3L1 complex for suppressor genes is becoming increasingly recognized. It is methylated DNA, has been used to detect cell type–dependent estimated that between 0.5% and 3% of all genes carrying CpG- differences in DNA methylation on a microarray platform. The rich promoter sequences (so-called CpG islands) may be silenced procedure has been verified and applied to identify a series of by DNA methylation in lung cancer (1, 11). This means that there novel candidate lung tumor suppressor genes and potential are most likely several hundred genes that are incapacitated by this DNA methylation markers that contain methylated CpG pathway. Some of these genes may be bona fide tumor suppressor islands. One gene of particular interest was DLEC1, located genes, but in other cases, the methylation event may be a at a commonly deleted area on chromosome 3p22-p21.3, consequence of gene silencing or may somehow be associated with which was frequently methylated in primary lung cancers and tumor formation rather than being a cause of tumorigenesis.
    [Show full text]
  • Pathogenetic Subgroups of Multiple Myeloma Patients
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector ARTICLE High-resolution genomic profiles define distinct clinico- pathogenetic subgroups of multiple myeloma patients Daniel R. Carrasco,1,2,8 Giovanni Tonon,1,8 Yongsheng Huang,3,8 Yunyu Zhang,1 Raktim Sinha,1 Bin Feng,1 James P. Stewart,3 Fenghuang Zhan,3 Deepak Khatry,1 Marina Protopopova,5 Alexei Protopopov,5 Kumar Sukhdeo,1 Ichiro Hanamura,3 Owen Stephens,3 Bart Barlogie,3 Kenneth C. Anderson,1,4 Lynda Chin,1,7 John D. Shaughnessy, Jr.,3,9 Cameron Brennan,6,9 and Ronald A. DePinho1,5,9,* 1 Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115 2 Department of Pathology, Brigham and Women’s Hospital, Boston, Massachusetts 02115 3 The Donna and Donald Lambert Laboratory of Myeloma Genetics, Myeloma Institute for Research and Therapy, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205 4 The Jerome Lipper Multiple Myeloma Center, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115 5 Center for Applied Cancer Science, Belfer Institute for Innovative Cancer Science, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 6 Neurosurgery Service, Memorial Sloan-Kettering Cancer Center, Department of Neurosurgery, Weill Cornell Medical College, New York, New York 10021 7 Department of Dermatology, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, 02115 8 These authors contributed equally to this work. 9 Cocorresponding authors: [email protected] (C.B.); [email protected] (J.D.S.); [email protected] (R.A.D.) *Correspondence: [email protected] Summary To identify genetic events underlying the genesis and progression of multiple myeloma (MM), we conducted a high-resolu- tion analysis of recurrent copy number alterations (CNAs) and expression profiles in a collection of MM cell lines and out- come-annotated clinical specimens.
    [Show full text]
  • Supplementary Table 1. Differentially Expressed Transcripts Between Insulin Treated (T) and Insulin Deprived (D) Type 1 Diabetic Patients
    Table Legends: Supplementary Table 1. Differentially expressed transcripts between insulin treated (T) and insulin deprived (D) type 1 diabetic patients. P values were calculated using paired t-tests, and not adjusted for multiple comparison errors. Annotations for each transcript were provided by Affymetrix NetAffx Analysis Center. Supplementary Table 2. Differentially expressed mitochondrial genes between insulin treated (T) and insulin deprived (D) type 1 diabetic patients. This EXCEL file has multiple data sheets. The data sheet “MITO GENE” lists the 68 mitochondrial genes, which were grouped into 11 functional groups in 11 data sheets. P values were calculated using paired t-tests, and not adjusted for multiple comparison errors. Annotations for each transcript were provided by Affymetrix NetAffx Analysis Center. OXPHOS- oxidative phosphorylation; TCA - tricarboxylic acid cycle. Supplementary Table 3. Differentially expressed pathways by Ingenuity Pathway Analysis (IPA). This EXCEL file has two data sheets that listed the significantly up- and down-regulated pathways in insulin-deprived vs. insulin- treated patients, respectively. P values associated with each pathway were calculated by IPA. Genes were represented by HUGO symbols. Supplementary Table 1 probe set T1 T2 T3 T4 T5 T6 T7 T8 214046_at 71.6231 78.4793 69.0236 71.6228 71.3996 61.9447 66.1693 61.9322 240081_at 145.816 133.058 155.18 126.734 137.149 130.863 157.818 127.17 227644_at 132.603 132.984 144.789 127.445 134.055 115.207 141.926 126.212 233926_at 13.1944 14.7052 12.8407
    [Show full text]
  • Susceptibility to Glaucoma: Differential Comparison of the Astrocyte
    Open Access Research2008LukasetVolume al. 9, Issue 7, Article R111 Susceptibility to glaucoma: differential comparison of the astrocyte transcriptome from glaucomatous African American and Caucasian American donors Thomas J Lukas¤*, Haixi Miao¤†, Lin Chen†, Sean M Riordan†, Wenjun Li†, Andrea M Crabb†, Alexandria Wise‡, Pan Du§, Simon M Lin§ and M Rosario Hernandez† Addresses: *Department of Molecular Pharmacology and Biological Chemistry, Feinberg School of Medicine, Northwestern University, E Chicago Ave, Chicago, IL 60611 USA. †Department of Ophthalmology, Feinberg School of Medicine, Northwestern University, E Chicago Ave, Chicago, IL 60611 USA. ‡Department of Biology, City College of New York, Convent Ave, New York, NY 10031, USA. §Robert H Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, E Chicago Ave, Chicago, IL 60611 USA. ¤ These authors contributed equally to this work. Correspondence: Thomas J Lukas. Email: [email protected] Published: 9 July 2008 Received: 9 May 2008 Revised: 18 June 2008 Genome Biology 2008, 9:R111 (doi:10.1186/gb-2008-9-7-r111) Accepted: 9 July 2008 The electronic version of this article is the complete one and can be found online at http://genomebiology.com/2008/9/7/R111 © 2008 Lukas et al.; licensee BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Abstract Background: Epidemiological and genetic studies indicate that ethnic/genetic background plays an important role in susceptibility to primary open angle glaucoma (POAG).
    [Show full text]
  • Identification of Dysregulated Genes in Rheumatoid Arthritis Based on Bioinformatics Analysis
    Identification of dysregulated genes in rheumatoid arthritis based on bioinformatics analysis Ruihu Hao1,*, Haiwei Du2,*, Lin Guo1, Fengde Tian1, Ning An1, Tiejun Yang3, Changcheng Wang1, Bo Wang1 and Zihao Zhou1 1 Department of Orthopedics, Affiliated Zhongshan Hospital of Dalian University, Dalian, China 2 Department of Bioinformatics, Beijing Medintell Biomed Co., Ltd, Beijing, China 3 Department of Orthopedics, Affiliated Hospital of BeiHua University, Jilin, China * These authors contributed equally to this work. ABSTRACT Background. Rheumatoid arthritis (RA) is a chronic auto-inflammatory disorder of joints. The present study aimed to identify the key genes in RA for better understanding the underlying mechanisms of RA. Methods. The integrated analysis of expression profiling was conducted to identify differentially expressed genes (DEGs) in RA. Moreover, functional annotation, protein– protein interaction (PPI) network and transcription factor (TF) regulatory network construction were applied for exploring the potential biological roles of DEGs in RA. In addition, the expression level of identified candidate DEGs was preliminarily detected in peripheral blood cells of RA patients in the GSE17755 dataset. Quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to validate the expression levels of identified DEGs in RA. Results. A total of 378 DEGs, including 202 up- and 176 down-regulated genes, were identified in synovial tissues of RA patients compared with healthy controls. DEGs were significantly enriched in
    [Show full text]
  • Genome-Wide Screening Identifies Genes and Biological Processes
    Louisiana State University LSU Digital Commons LSU Doctoral Dissertations Graduate School 10-12-2018 Genome-Wide Screening Identifies Genes and Biological Processes Implicated in Chemoresistance and Oncogene-Induced Apoptosis Tengyu Ko Louisiana State University and Agricultural and Mechanical College, [email protected] Follow this and additional works at: https://digitalcommons.lsu.edu/gradschool_dissertations Part of the Cancer Biology Commons, Cell Biology Commons, and the Genomics Commons Recommended Citation Ko, Tengyu, "Genome-Wide Screening Identifies Genes and Biological Processes Implicated in Chemoresistance and Oncogene- Induced Apoptosis" (2018). LSU Doctoral Dissertations. 4715. https://digitalcommons.lsu.edu/gradschool_dissertations/4715 This Dissertation is brought to you for free and open access by the Graduate School at LSU Digital Commons. It has been accepted for inclusion in LSU Doctoral Dissertations by an authorized graduate school editor of LSU Digital Commons. For more information, please [email protected]. GENOME-WIDE SCREENING IDENTIFIES GENES AND BIOLOGICAL PROCESSES IMPLICATED IN CHEMORESISTANCE AND ONCOGENE- INDUCED APOPTOSIS A Dissertation Submitted to the Graduate Faculty of the Louisiana State University and Agricultural and Mechanical College in partial fulfillment of the requirements for the degree of Doctor of Philosophy in Biomedical and Veterinary Medical Sciences through the Department of Comparative Biomedical Sciences by Tengyu Ko B.S., University of California, Santa Barbara 2010 December 2018 ACKNOWLEDGEMENTS I would like to express my sincerest gratitude to my major supervisor Dr. Shisheng Li for giving me the opportunity to join his team and the freedom to pursue projects. I appreciate all of his thoughts and efforts. Truly, none of these findings would be possible without his supervisions, supports, insightful discussions, and patience.
    [Show full text]